MicroRNA-203 contributes to skin re-epithelialization

Abstract

Keratinocyte proliferation and migration are crucial steps for the rapid closure of the epidermis during wound healing, but the molecular mechanisms involved in this cellular response remain to be completely elucidated. Here, by in situ hybridization we characterize the expression pattern of miR-203 after the induction of wound in mouse epidermis, showing that its expression is downregulated in the highly proliferating keratinocytes of the ‘migrating tongue', whereas it is strongly expressed in the differentiating cells of the skin outside the wound. Furthermore, subcutaneous injections of antagomiR-203 in new born mice dorsal skin strengthened, in vivo, the inverse correlation between miR-203 expression and two new target mRNAs: RAN and RAPH1. Our data suggest that miR-203, by controlling the expression of target proteins that are responsible for both keratinocyte proliferation and migration, exerts a specific role in wound re-epithelialization and epidermal homeostasis re-establishment of injured skin.

Tumor suppressor function of miR-483-3p on squamous cell carcinomas due to its pro-apoptotic properties

“…49 Interestingly, RAN is also targeted by miR-203, whose expression is decreased in healing epidermis, thus favoring keratinocytes migration and proliferation. 50 Finally, despite that API5 was previously shown (1) to protect cells from growth factor deprivation-or drug-induced apoptosis 51,52 and (2) to be targeted by other miRNAs, 53,54 it seemed non-essential for the pro-apoptotic effects of miR-483-3p. Indeed, in our hands, API5 knockdown did not affect BCL2 expression and did not induce caspase 3 activity following serum removal.…”

“…Other "wound-healing miRNAs" such as miR-198 and miR-203 could also fulfill these requisites. miR-198 and miR-203 are downregulated following skin injury and allow the keratinocyte migration and proliferation necessary to wound closure, 50,55 suggesting that an ectopic expression of these miRNAs could limit tumorigenesis. Indeed, miR-203 has recently been shown to be a tumor suppressor in basal cell carcinoma, 56 and decreased miR-198 expression is observed in hepatocellular carcinomas, where it favors tumor cells growth and invasion.…”

p63 supports aerobic respiration through hexokinase II

“…ΔNp63 has a crucial role in counteracting cellular senescence and organismal aging through its support of the proliferating potential of epithelial cells (5,24,(33)(34)(35)(36)(37). Therefore, ΔNp63 could exert its antisenescence/antiaging functions, at least in part, through the activation of the HK2 gene, thus supporting mitochondria functions.…”

microRNA-203 Modulates Wound Healing and Scar Formation via Suppressing Hes1 Expression in Epidermal Stem Cells

“…This effect was associated with increased re-epithelialization, skin attachment regeneration, and collagen reassignment, likely due to inhibition of differentiation of ESCs to MFB. In addition to miR-203, several other miRNAs, such as miR-21, miR-34, and miR146a/b are also involved in regulation of cell differentiation and proliferation in skin development [51][52][53][54]. Therefore, a reasonable hypothesis is that dysregulation of miRNA expression critically contributes to the wound healing processes and scar formation.…”